Faculty of
Medicine
Medical Education-
Damietta
University
Level 3
Semester 6
Module Surgery I
Learning Outcomes
By the end of the lecture, the students will be able to:
1. Enumerate risk factors for breast cancer.
2. Describe the pathology of breast cancer.
Breast cancer
Breast cancer is the most common cause of death in middle-aged women in
Western countries.
In Egypt the disease is common, and it affects women in a younger age group.
It accounts for 35% of total malignancies among Egyptian females.
It is the second leading cause of cancer death.
However, mortality from breast cancer is declining due to better screening and
adjuvant treatment
Scope of the problem
In 2020, there were2.3 million women diagnosedwith breast cancer
and685,000 deaths globally.
At the end of 2020, there were7.8 million women alivewho were diagnosed
with breast cancer in the past 5 years, making it the world’s most prevalent
cancer.
Breast cancer occurs in every country of the world in women at any age after
puberty but withincreasing rates in later life.
Risk factors
•A
•R
•M
• Obese
• Has a history
• Say a quota
Who is at risk? Identifiable risk factors
• Breast cancer and hereditary factors:
A. BRCA I and BRCA II genes have been found in the long arm of chromosome 17 and 13 respectively in women
with a family history of carcinoma of the breast.
A. BRCA I and BRCA 2 are the genes associated with increased risk.
B. BRCA I and II mutations are more common in Ashkenazi Jews.
C. They are more prone to ovarian cancer also.
D. Hence all patients with BRCA I and BRCA II mutations should consider a prophylactic bilateral
oophorectomy after childbearing is completed, with bilateral mastectomy.
Who is at risk? Identifiable risk factors
• Breast cancer and hereditary factors:
B. Cowden's disease (multiple hamartoma syndrome);
• Associated with reduced tumor suppressor gene PTEN.
• 30-50% of patients will develop breast cancer by 50 years of age.
• The lesions found in this syndrome are multiple facial trichilemmomas
(pathognomonic), oral papilloma, bilateral breast cancer, haemangiomas, lipomas,
thyroid tumours, etc.
C. Ataxia-telangiectasia: It is associated with haemangioma and carcinoma breast.
Who is at risk? Identifiable risk factors
• Breast cancer and hereditary factors:
• Li-Fraumeni syndrome is a rare disease with familial breast cancer and is
associated with an inherited mutation of tumour suppressor P53 gene.
• It is a rare autosomal dominant disorder.
• 90% of carriers will develop breast cancer by the age of 50.
• They also can have other tumours in childhood such as soft tissue sarcoma,
osteosarcoma, and leukaemia.
Who is at risk? Identifiable risk factors
• History of breast cancer:
▪ The risk of developing second breast cancer is about 0.5 to 0.7% in women with
previous invasive breast cancers.
▪ Breast cancer is 3 to 4 times more likely to develop in women with a first-degree
relative who had breast cancer.
▪ This risk is further increased if they have premenopausal and bilateral cancer.
▪ Women with ductal carcinoma in situ (DCIS) are at an increased risk of developing
ipsilateral and contralateral breast cancers (4.1 % after 5 years).
Who is at risk? Identifiable risk factors
Benign breast disease:
▪ In general, proliferative breast lesions are more vulnerable for
malignancy.
▪ Non-proliferative lesions such as cysts and duct ectasia do not
increase the risk of breast cancer.
Who is at risk? Identifiable risk factors
• Chest wall radiation:
• Young children/women who have received mantle radiation for Hodgkin's disease
have increased risk (19%) by the age of 50.
• Geographical:
• Carcinoma of the breast is the disease of white, western women.
• It is rare in Japan and Taiwan.
• Genetic predisposition exists in a few cases, especially in bilateral breast carcinoma.
The location of the tumors within the breast
• Upper outer quadrant (most commonly affected quadrant) 25%
• Lower outer quadrant 5%.
• Upper inner quadrant 8%.
• Lower inner quadrant 4%.
• Central portion 4%.
• Axillary tail 1%
• Overlapping 52%
Multicentricity and multifocality
• Multicentricity is defined as two or more tumours occurring in more than
one breast quadrant simultaneously.
• Normal breast tissue must intervene between tumours.
• Multifocality is defined as separate foci of tumours occurring within the
same breast quadrant.
• Multifocal disease can be treated by conservative surgery, while
Multicenteric lesion mostly needs mastectomy.
Pathology of breast cancer
• Breast cancer arises in;
• The lining cells (epithelium) of the ducts (85%) or
• Lobules (15%) in the glandular tissue of the breast.
• Initially, the cancerous growth is confined to the duct or lobule (“in situ”)
where it generally causes no symptoms and has minimal potential for
spread (metastasis).
Pathology of breast cancer
• Over time, these in situ (stage 0) cancers may progress and invade the
surrounding breast tissue (invasive breast cancer) and then spread to
the nearby lymph nodes (regional metastasis) or other organs in the
body (distant metastasis).
Pathology of breast cancer
• If a woman dies from breast cancer, it is because of widespread metastasis.
• Almost all breast cancers are adenocarcinomas.
• Breast cancer may be non-invasive (in situ), invasive or mixed.
• It can be well-differentiated, moderately differentiated, or poorly
differentiated.
Ductal carcinoma:
Breast cancer • Ductal carcinoma in situ.
can be • Invasive ductal carcinoma
classified (commonest type of breast
into: cancer).
Lobular carcinoma:
• Lobular carcinoma in situ.
• Invasive lobular carcinoma.
This lesion is usually detected in screening
programs as mammographically visible
microcalcification.
Ductal It accounts for 20% of cancers detected by
screening.
carcinoma
in situ Most patients present with DCIS in early
menopausal years.
The risk of development of invasive cancer from
DCIS ranges from 30-50% over 10 years.
This disease affects women ofslightly older age
group.
Paget’s disease It is a specific form ofintraductal carcinomathat
involves the main lactiferous ducts, but it extends
of the nipple to infiltrate the overlying nipple and the areola.
Therefore, Paget's disease of the nipple
isa superficialmanifestation of an underlying
breast carcinoma.
Paget’s disease of the nipple
• It presents with an eczema-like lesion of the nipple and areola, with
fissuring, ulceration, and oozing which persist in spite of local treatment.
• The nipple erodes slowly and eventually disappears.
• If untreated, the underlying carcinoma will eventually become clinically
evident.
• Thus nipple eczema should biopsied if there is any doubt about its cause
Paget’s disease of the nipple
• Microscopically it is characterized by the presence of Paget’s cells,
(large ovoid cells with clear vacuolated cytoplasm and small dark
staining nuclei).
Invasive ductal carcinoma
Invasive ductal (commonest type of breast cancer)
carcinoma
This occurs when DCIS invades the
(commonest basement membrane.
type of breast
cancer) It has different morphological types;
some have prognostic importance.
This is the most common type of breast
cancer.
Invasive duct
carcinoma not
otherwise It is composed of a heterogenous group
specified (NOS) of tumor cells that do not demonstrate
morphologic features of any of the
special types of breast cancer, that is
why it is called non-otherwise specified.
The tumour is usuallyhardin consistency and
it gives a gritty sensation when it is cut.
The cut surface is concave andgreyin color
Invasive ductal with prominent yellow and white flecks.
carcinoma It is characterized byearly lymphatic
spreadandpoorprognosis.
Presence of lymphatic, vascular or perineural
spreadworsensthe prognosis.
Rare types of infiltrating ductal
carcinoma
• Mucinous carcinoma
• is also called colloid, mucoid, gelatinous or mucin-secreting carcinoma.
• Usually, it occurs above the age of 45, in the form of a smooth rounded soft retro areolar mass of 1-
4cm diameter, with a glistening cut surface.
• Microscopically it is in the form of a pool of mucinous material with aggregates of cancer cells.
• Papillary carcinoma;
• Histologically demonstrates papillary formation and it presents by bleeding per nipple.
• As this tumour is well delineated from surrounding breast tissue by fibrous covering it was called
intracystic papillary carcinoma.
Lobular carcinoma
• Lobular carcinoma in situ
• Lobular carcinoma in situ is usually diagnosed accidentally while doing biopsy
for another breast lesion.
• It has 3 types; classic, pleomorphic, and florid.
• Classic type doesn’t need excision, only follow-up.
• While the pleomorphic and florid types should be excised if they were
diagnosed in biopsy.
Lobular carcinoma
• Invasive lobular carcinoma
• Lobular carcinoma may occur bilaterally.
• It is similar in behavior and prognosis to ductal carcinoma; however they are
characterized by:
• They are difficult to be seen on mammography
• They usually present in late stages
• Linear arrangement of cells, the so called “Indian filing”.
Hormone receptors in breast cancer
• More than 60% of breast cancers carry hormone receptors in or on their cells.
• Important hormone receptors in breast cancer are:
▪ Estrogen receptors (ER)
▪ Progesterone receptors (PR)
▪ Human epidermal growth factor receptor (Her-2/neu)
• Hormone receptor status is routinely assessed in breast cancer specimens because
the result can modify the treatment plan and it is of prognostic significance.
ER and PR positivebreast cancer havegoodprognosis and
they can be treated by adjuvant hormonal therapy with
tamoxifen or the newer aromatase inhibitors.
Her-2/neu positive tumoursare associated with increased
incidence of recurrence and shortened overall survival.
Significance of
• Her-2/neu positive tumourscan be treated with the monoclonal
hormone antibody trastuzumab (Herceptin)
receptors
Triple negative breast cancer
• Carries a poor prognosis.
• It cannot be targeted by endocrine therapy or anti HER2 agents.
• It is seen more commonly in younger women and in African races.
• It accounts for 15-20% of sporadic breast cancers, and 70-80% of
hereditary breast cancer caused by BRCA1 germ-line mutations.
Local spread:
• The tumour grows in size and invades the surrounding tissues as the skin,
pectoral fascia, underlying muscles and chest wall.
Lymphatic spread:
• occurs by embolism or permeation primarily to axillary and internal mammary
nodes. In advanced cases, lymphatic spread reaches the supraclavicular nodes.
Spread of breast The site of the tumour does not dictate which nodes will be
cancer involved.
Nodal spread is considered a marker of metastatic potential
and it is an important poor prognostic factor.
Blood spread:
• to liver, lungs, bones and brain. Skeletal metastases are osteolytic and they
most commonly affect lumbar and dorsal vertebrae, femur, ribs and skull.
